Randomized controlled trials have shown that ≤100 mg aspirin daily is not effective for primary prevention of cardiovascular events in diabetes; however, clinical and pharmacologic evidence suggests these patients need >100 mg for adequate antiplatelet activity. Although high on-treatment platelet reactivity (HTPR) could explain the lack of benefit, prevalence of HTPR in diabetes is not known. This systematic review examined the relationship between daily aspirin dose and prevalence of HTPR in patients with diabetes.

Three electronic databases were searched until May 2013 using database-appropriate terms for aspirin, resistance, and diabetes. Studies were included if prevalence of HTPR was reported according to daily dose and diabetes status. Patients were stratified by daily aspirin dose and the weighted mean prevalence across studies was calculated. Where appropriate, pooled relative risks (RR) were calculated using a random-effects model.

Data were available from 31 studies that enrolled 2147 diabetic patients. Overall, prevalence of HTPR was 21.9% (95% confidence interval [CI], 15.2%-28.5%) in diabetic patients and 15.8% (95% CI, 11.4%-20.3%) in nondiabetic patients (pooled RR 1.36; 95% CI, 1.08-1.71; I² 56%). Prevalence appeared to be dose related, with 398 (23.6%) of 1689 diabetic patients using ≤100 mg daily having HTPR compared with 64 (12.3%) of 518 diabetic patients using 101-325 mg daily (pooled RR 1.70; 95% CI, 1.07-2.72; I² 0%).

Although these observations should be verified in a clinical trial, the possibility that 1 in 4 patients have HTPR with doses commonly used in diabetes could have significant implications on overall effectiveness of aspirin.